Synthesis of a novel class of substituted benzothiophene or benzofuran derivatives as BMP-2 up-regulators and evaluation of the BMP-2-up-regulating effects in vitro and the effects on glucocorticoid-induced osteoporosis in rats.

Abstract

The BMP pathway is a promising new target for the design of therapeutic agents for the treatment of low bone mass. To enrich our understanding of SAR and based on our previously concluded structure-effect relationship, 23 derivatives were prepared in this work. The synthesis, up-regulating activities on BMP-2 expression, and bone loss prevention efficacies of these compounds in rats with glucocorticoid-induced osteoporosis are presented. The bone histology of the tested rats assessed through light microscopy showed that compounds 1, 21, 35, and 38 significantly increased the trabecula compared with the model group, and the trabecula of the groups treated with 8a was similar to that obtained with raloxifene and alfacalcidol. The compounds exhibited potential for development as anabolic agents.

• Authors: Si-tu Xue, Hui-fang Guo, Mei-jie Liu, Jie Jin, Da-hong Ju, Zong-ying Liu, Zhuo-rong Li
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 96 Pg. 151-61 ( 2015) ISSN: 1768-3254 [Electronic] France
• PMID: 25874339 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Chemical References

• BMP2 protein, human
• Benzofurans
• Bone Morphogenetic Protein 2
• Glucocorticoids
• Thiophenes
• benzothiophene
• benzofuran

Topics

• Animals
• Benzofurans (chemical synthesis, chemistry, pharmacology)
• Bone Morphogenetic Protein 2 (biosynthesis, metabolism)
• Cell Line
• Female
• Glucocorticoids
• Male
• Mice
• Mice, Inbred Strains
• Osteoporosis (chemically induced, drug therapy, metabolism)
• Rats
• Rats, Wistar
• Thiophenes (chemical synthesis, chemistry, pharmacology)
• Up-Regulation (drug effects)